Efficacy and safety of baroreflex activation therapy for heart failure with reduced ejection fraction: systematic review.

Baroreflex activation therapy (BAT) is a possible adjuvant treatment for patients with heart failure with reduced ejection fraction (HFrEF) who remain symptomatic despite optimal medical therapy and may be an alternative therapy in patients with contraindications or drug intolerance. Our aim was to evaluate the efficacy and safety of BAT in patients with HFrEF. The protocol for this study was registered with PROSPERO (CRD42022349175). Searches were conducted using MEDLINE, preMedLine (via PubMed), EMBASE, Cochrane Library, Web of Science, Trip Medical Database, WHO International Clinical Trials Registry, and ClinicalTrials.gov. We included randomized controlled trials that compared the effects of BAT with pharmacological treatment. We assessed the risk of bias of each study using the Cochrane RoB2 tool and the certainty of the results using the GRADE approach. We performed a meta-analysis of treatment effects using a fixed-effects or random-effects model, depending on the heterogeneity observed. Two studies were included in the meta-analysis (HOPE4HF and BeAT-HF). The results showed that BAT led to statistically significant improvements in New York Heart Association functional class (relative risk 2.13; 95% confidence interval [CI, 1.65 to 2.76]), quality of life (difference in means -16.97; 95% CI [-21.87 to -12.07]), 6 min walk test (difference in means 56.54; 95% CI [55.67 to 57.41]) and N-terminal probrain natriuretic peptide (difference in means -120.02; 95% CI [-193.58 to -46.45]). The system- and procedure-related complication event-free rate varied from 85.9% to 97%. The results show that BAT is safe and improves functional class, quality of life and congestion in selected patients with HFrEF. Further studies and long-term follow-up are needed to assess efficacy in reducing cardiovascular events and mortality.

An innovative framework to determine the implementation level of personalized medicine: A systematic review.

Background: Personalized medicine (PM) is now the new frontier in patient care. The application of this new paradigm extends to various pathologies and different patient care phases, such as diagnosis and treatment. Translating biotechnological advances to clinical routine means adapting health services at all levels is necessary. Purpose: This article aims to identify the elements for devising a framework that will allow the level of PM implementation in the country under study to be quantitatively and qualitatively assessed and that can be used as a guideline for future implementation plans. Methods: A systematic review was conducted per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The research question was: What are the domains for determining the level of implementation of PM at the national level? The domains for assessing the degree of PM implementation, which would form the framework, were established. Results: 19 full-text studies that met the inclusion criteria were peer-selected in the systematic review. From all the studies that were included, 37 elements-encompassed in 11 domains-were extracted for determining the degree of PM implementation. These domains and their constituent elements comprise the qualitative and quantitative assessment framework presented herein. Each of the elements can be assessed individually. On the other hand, the domains were standardized to all have the same weight in an overall assessment. Conclusions: A framework has been developed that takes a multi-factorial approach to determine the degree of implementation of PM at the national level. This framework could also be used to rank countries and their implementation strategies according to the score they receive in the application of the latter. It could also be used as a guide for developing future national PM implementation strategies. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022338611, Identifier: CRD42022338611.

Barriers for the evaluation of advanced therapy medicines and their translation to clinical practice: Umbrella review.

Advanced therapy medicinal products (ATMPs) are a fast-growing field of medicine with wide potential application. Nevertheless, so far, only 19 have obtained European Union (EU) marketing authorisation and only 13 of these have translated successfully into clinical practice. This study conducts an umbrella review to identify the main barriers for the evaluation of ATMPs and their translation into clinical practice across the development lifecycle. 71 systematic reviews were included, of which 50 dealt primarily with effectiveness and safety, 13 with translation from pre-clinical to human subjects. Others dealt with economic issues and translation from health technology assessment to market access. The literature highlights the importance of synergistic research groups or networks that collaborate across the in-vitro science, preclinical and clinical investigation phases, and the role of private investor capital and public-private collaborations. Most ATMPs reviewed seem to have a favourable safety profile although considerable uncertainties remain. Randomised controlled trials are not always feasible in these patient groups. Greater sharing of data is recommended, both at preclinical and post-marketing real world evidence. There are considerable variations between EU countries in how they regulate hospital exemption for ATMPs, and this can lead to inequitable access for patients.

Diagnostic accuracy of optical coherence tomography angiography in the detection of neovasculature in age-related macular degeneration: a meta-analysis.

This work is a systematic review and meta-analysis to evaluate the diagnostic accuracy of optical coherence tomography angiography (OCTA) in the identification of choroidal neovascularization due to age-related macular degeneration (AMD) in comparison with fluorescein angiography (FA). A systematic search of the literature was carried out on Medline, EMBASE, Web of Science, Cochrane Library and Center for Reviews and Dissemination. Studies comparing OCTA with FA for the diagnosis of choroidal neovascularization due to AMD that included data on the diagnostic validity of the test or the data necessary for its calculation were selected. The QUADAS-2 tool was used to assess the risk of bias in selected studies. The quantitative analysis of the results was performed by meta-analysis. Seven primary studies were included. The quality of the evidence was good. The total population included in the meta-analysis comprised 553 eyes, with a cumulative sensitivity and specificity of 85.9% (95% CI 81.9-89.3%) and 89% (95% CI 83.5-93.2%), respectively, cumulative positive and negative likelihood ratios of 8.36 and 0.15, respectively (95% CI of 3.05-22.890 and 0.09-0.24, respectively), and a cumulative diagnostic odds ratio of 67.21 (95% CI 22.58-200.05). The evidence obtained does not demonstrate the superiority of OCTA over FA. Its use as a support technique could improve patient flow and reduce the number of FA.

Efficacy and safety of home-based exercises versus individualized supervised outpatient physical therapy programs after total knee arthroplasty: a systematic review and meta-analysis.

PURPOSE: The aim of the present study was to evaluate the efficacy and safety of non-supervised home-based exercise versus individualized and supervised programs delivered in clinic-based settings for the functional recovery immediately after discharge from a primary TKA. METHODS: Medline, Embase, Cochrane, and PEDro databases were screened, from inception to April 2015, in search for randomized clinical trials (RCT) of home-based exercise interventions versus individualized and supervised outpatient physical therapy after primary TKA. Target outcomes were: knee range of motion (ROM), patient-reported pain and function, functional performance, and safety. Risk of bias was assessed with the PEDro scale. After assessing homogeneity, data were combined using random effects meta-analysis and reported as standardized mean differences or mean differences. We set a non-inferiority margin of four points in mean differences. RESULTS: The search and selection process identified 11 RCT of moderate quality and small sample sizes. ROM active extension data suitable for meta-analysis was available from seven studies with 707 patients, and ROM active flexion from nine studies with 983 patients. Most studies showed no difference between groups. Pooled differences were within the non-inferiority margin. Most meta-analyses showed significant statistical heterogeneity. CONCLUSION: Short-term improvements in physical function and knee ROM do not clearly differ between outpatient physiotherapy and home-based exercise regimes in patients after primary TKA; however, this conclusion is based on a meta-analysis with high heterogeneity. LEVEL OF EVIDENCE: I.

Revisión sistemática de la literatura sobre la osteonecrosis maxilar con el uso de bisfosfonatos en pacientes con osteoporosis / Systematic literature review of bisphosphonates and osteonecrosis of the jaw in patients with osteoporosis

Objetivo. Evaluar sistemáticamente la literatura en relación con la aparición de osteonecrosis de mandíbula (ONM) con el uso de bisfosfonatos (BF) en el tratamiento de la osteoporosis (OP). Métodos. Se realizó una búsqueda sistemática de la literatura en Pubmed, EMBASE y la Cochrane Central Register of Controlled Trials hasta julio de 2010 incluyendo términos relativos a OP, ONM, y BF (mesh y texto libre). Se seleccionaron metaanálisis, revisiones sistemáticas y ensayos clínicos (EC), en inglés o español, que incluían pacientes>18 años de ambos sexos con OP en tratamiento con BF (por vías intravenosa y oral). Además, los estudios debían evaluar la aparición de ONM durante el tratamiento con BF. Se excluyeron los estudios que incluían pacientes con cáncer u otra enfermedad distinta de la OP, estudios en animales y ciencia básica. La selección de los artículos, tanto por título y abstract como la revisión en detalle, la realizaron 2 revisores de forma independiente. Se utilizó la escala de Oxford modificada (versión del 2001) para evaluar la calidad de los estudios incluidos. Resultados. Se identificaron 1.422 artículos, de los que se incluyeron 18 (8 revisiones sistemáticas, 8 EC y 2 metaanálisis). La mayoría de los estudios son de buena calidad y estudiaron el uso de BF en mujeres de mediana edad con OP. La frecuencia de ONM fue baja. Conclusiones. No hemos encontrado evidencia suficiente para afirmar que los BF por vía oral ni intravenosa utilizados exclusivamente para el tratamiento de la OP confieran un riesgo significativo de ONM al paciente (nivel de evidencia 2a, grado de recomendación B)(AU)

Objective: To systematically assess the literature related to the occurrence of osteonecrosis of the jaw (ONJ) using bisphosphonates (BP) in the treatment of osteoporosis (OP). Methods: We conducted a systematic literature search in PubMed, EMBASE and the Cochrane Central Register of Controlled Trials up to July 2010, including terms relating to OP, ONJ, and BP (MeSH and free text). We selected meta-analysis, systematic reviews and clinical trials (CT), English or Spanish, including patients > 18 years of both sexes with OP treated with BF (intravenous and oral). Furthermore, studies should evaluate the occurrence of ONJ during treatment with BF. We excluded studies that included patients with cancer or diseases other than OP, animal studies and basic science. The selection of articles both by title and 2 independent reviewers conducted a detailed review of the abstracts. We used the modified Oxford Scale (version 2001) to assess the quality of the included studies. Results: We identified 1422 articles of which we included 18 (8 systematic reviews, 8 CT and 2 metaanalysis). Most studies were of good quality and examined the use of BF in middle-aged women with OP. Frequency of ONJ was low. Conclusions: We found insufficient evidence to affirm that intravenous or oral BF used exclusively for the treatment of OP lead to a significant risk of ONJ (evidence level 2a, grade B recommendation)(AU)

Systematic literature review of bisphosphonates and osteonecrosis of the jaw in patients with osteoporosis.

OBJECTIVE: To systematically assess the literature related to the occurrence of osteonecrosis of the jaw (ONJ) using bisphosphonates (BP) in the treatment of osteoporosis (OP). METHODS: We conducted a systematic literature search in PubMed, EMBASE and the Cochrane Central Register of Controlled Trials up to July 2010, including terms relating to OP, ONJ, and BP (MeSH and free text). We selected meta-analysis, systematic reviews and clinical trials (CT), English or Spanish, including patients > 18 years of both sexes with OP treated with BF (intravenous and oral). Furthermore, studies should evaluate the occurrence of ONJ during treatment with BF. We excluded studies that included patients with cancer or diseases other than OP, animal studies and basic science. The selection of articles both by title and 2 independent reviewers conducted a detailed review of the abstracts. We used the modified Oxford Scale (version 2001) to assess the quality of the included studies. RESULTS: We identified 1422 articles of which we included 18 (8 systematic reviews, 8 CT and 2 meta-analysis). Most studies were of good quality and examined the use of BF in middle-aged women with OP. Frequency of ONJ was low. CONCLUSIONS: We found insufficient evidence to affirm that intravenous or oral BF used exclusively for the treatment of OP lead to a significant risk of ONJ (evidence level 2a, grade B recommendation).